Adiponectin is a major insulin sensitizing hormone, which activates AMP kinase and PPARα pathways to facilitate glucose and lipid metabolism to increase insulin sensitivity. Decreased plasma adiponectin linked to obesity is causally involved in insulin resistance and metabolic syndrome in obesity. Moreover, decreased plasma adiponectin is causally involved in atherosclerosis. In fact, decreased plasma adiponectin levels have been shown to be associated with future development of diabetes and cardiovascular diseases in humans. These biological effects of adiponectin are mediated via adiponectin receptors, AdipoR1 and AdipoR2. Activation of AdipoR1 by adiponectin stimulates AMP kinase pathway and that of AdipoR2 by adiponectin stimulates PPARα pathway, thereby ameliorating insulin resistance. AdipoR1 and AdipoR2 are down-regulated in obesity, which is also casually involved in insulin resistance linked to obesity. PPARγ agonists upregulate plasma adiponectin levels, which contributes to amelioration of insulin resistance and atherosclerosis. On the other hand, PPARα agonists upregulate adiponectin receptors. Recently, adiponectin has been shown to stimulate AMPK activity in the arcuate hypothalamus and increase food intake via AdipoR1. Moreover, adiponectin decreases energy expenditure. Adiponectin appears to serve as a starvation gene. Thus adiponectin is upregulated according to decreased white adipose tissue mass, which then centrally facillitates energy storage and peopherally facillitates fatty acid combustion to generate energy for survival. In times of plenty, adiponectin is downregulated according to increased white adipose tissue mass, namely obesity, thereby causing insulin resistance, diabetes, and the metabolic syndrome. Thus, adiponectin and adiponectin receptors are crucially involved in the development of insulin resistance, diabetes, metabolic syndrome, and obesity and thus may serve as molecular targets of treatment and prevention strategy of these diseases.
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